This project will examine in human cocaine users the interactions of cocaine with drugs currently used or proposed for use in the treatment of cocaine abuse. In addition, the project will examine the effects of cocaine in methadone maintenance patients, a population at high risk for cocaine abuse. The project aims to identify potentially beneficial (e.g., efficacy in blockade of cocaine effects) and potentially harmful (e.g., changes in cardiovascular function or increases in cocaine-induced euphoria) effects produced when cocaine is self-administered during treatment with pharmacological agents. In a residential human experimental laboratory the physiological, subjective, and behavioral effects of cocaine challenge alone and in combination with a test drug will be intensively studied under controlled double-blind conditions. In the first study the effects of cocaine alone will be compared in methadone-dependent cocaine abusers and in non-opioid using cocaine abusers. Studies to examine the effect of repeated administration of two antidepressants, desipramine and trazodone, on response to cocaine challenge will then be conducted in methadone maintenance patients who abuse cocaine. A second group of studies will examine the interaction between cocaine and drugs proposed for use in cocaine abuse treatment (haloperidol, bromocriptine, amantadine, and 1-dopa) in non-opioid dependent cocaine abusers. These experiments will provide multifaceted data concerning the safety and efficacy of various pharmacological agents in a population at high risk for self-administration of cocaine and may provide information on which to base decisions about the treatment of cocaine abusers.